Reactive Donor Research Articles

Prevalence of transfusion-transmitted infection and reactive donor response rate in a tertiary care hospital in South India: A retrospective observational study

Abstract Background: Transfusion-transmitted infections (TTIs) are a serious problem to our blood centers as they necessitate utilization of massive resources and labor to detect and remove infected blood donations and also turn out to be a source of great distress to the patients recieving blood components and the doctors treating them. The main diseases that are made mandatory by the government to be screened are hepatitis B virus, hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis. Adding to this, India does not have a centralized donor notification system to notify the donors of their TTI positivity status causing the blood centers to be blind and not having a system to verify the credentials of donors making sure they were not tested positive in other centers in the country. Materials and Methods: We have done a retrospective study that aims to analyze blood center samples and look for the number of TTI positivity in our donations and compare with the total number of donations during the period of January 2016 to March 2023. The data were collected from the blood donor questionnaire and data were put up in an Excel sheet which was later analyzed on the Statistical P program. Results: During the study period, 14,257 donors donated blood. Of which 11,674 (83%) were voluntary donors and 2413 (17%) were replacement donors. About 98.7% were male donors. Among the total donors, 182 (1.27%) were positive for transfusion-transmitted infections. Among the 182 serology-positive donors, 179 (98.3%) were males and 3 (1.7%) were females. Among the 14,257 donors, 160 (1.12%) were positive for hepatitis B surface antigen (HbsAg), 2 (0.014%) for HCV, 2 (0.014%) for HIV, and 18 (0.126%) for syphilis. Among the 182 positive TTI, 160 (87.9%) donors were positive for HBsAg, 18 (9.9%) were positive for syphilis, 2 (1.1%) donors with HIV, and 2 (1.1%) with HCV positivity. Among the 182 donors positive for TTI, 81 (44.5%) donors had donated previously in various hospitals and they were not aware of their positive status. Conclusion: This study mainly aims to bring awareness to the problems that blood centers face in TTI from having to screen every sample to independently verifying donors making sure that they have never tested positive for TTI and counseling them on further tests and referrals.

Reactive Blood Donor Notification and Counselling – A Single Centre Experience.

Reactive Blood Donor Notification and Counselling – A Single Centre Experience.

PRDX6 augments selenium utilization to limit iron toxicity and ferroptosis.

Ferroptosis is a form of regulated cell death induced by iron-dependent accumulation of lipid hydroperoxides. Selenoprotein glutathione peroxidase 4 (GPX4) suppresses ferroptosis by detoxifying lipid hydroperoxides via a catalytic selenocysteine (Sec) residue. Sec, the genetically encoded 21st amino acid, is biosynthesized from a reactive selenium donor on its cognate tRNA[Ser]Sec. It is thought that intracellular selenium must be delivered 'safely' and 'efficiently' by a carrier protein owing to its high reactivity and very low concentrations. Here, we identified peroxiredoxin 6 (PRDX6) as a novel selenoprotein synthesis factor. Loss of PRDX6 decreases the expression of selenoproteins and induces ferroptosis via a reduction in GPX4. Mechanistically, PRDX6 increases the efficiency of intracellular selenium utilization by transferring selenium between proteins within the selenocysteyl-tRNA[Ser]Sec synthesis machinery, leading to efficient synthesis of selenocysteyl-tRNA[Ser]Sec. These findings highlight previously unidentified selenium metabolic systems and provide new insights into ferroptosis.

Donor notification and impact of counselling of reactive blood donors in the blood centre of a tertiary care teaching hospital of Odisha in eastern India

To ensure blood safety in blood transfusion service, the practice of donor screening, donor notification and counselling is essential. The aim of the study was to analyse the response rate of notified reactive donors to counselling and to see the impact of donor notification on reactive donors. A observational descriptive cross-sectional study was conducted in the blood centre of department of Transfusion Medicine, MKCG Medical College and Hospital Berhampur, Odisha during the time period from January 2022 to December 2022. Data was collected from reactive blood donor counselling register. Sero-reactive donors were contacted telephonically. Those who turned up into blood centre were counselled again and referred to appropriate centre for further management. The statistical analysis was done using percentages based on descriptive analysis.Out of total 32700 donations over a period of one year, 726 (2.22%) were reactive donors. Out of the total 726 donors, 496 (68.31%) donors could be notified telephonically, rest 230 could not be notified due to several reasons. Out of 496, 352(48.48%) were responders, who were counselled and referred to higher centres for further management. The response rate was 48.48%. Only 24 sero-reactive donors could be followed up. Pre-donation counselling, appropriate TTI screening test, donor notification and post donation counselling all together form a vital link between blood donors and blood safety, however the gap still exists.

Blood donation screening for hepatitis B virus core antibodies: The importance of confirmatory testing and initial implication for rare blood donor groups.

Exclusion of blood donors with hepatitis B virus (HBV) core antibodies (anti-HBc) prevents transfusion-transmitted HBV infection but can lead to significant donor loss. As isolated anti-HBc positivity does not always indicate true past HBV infection, we have investigated the effectiveness of confirmatory anti-HBc testing and the representation of rare blood groups in anti-HBc-positive donors. Three hundred ninety-seven HBV surface antigen-negative and anti-HBc initially reactive blood donor samples were tested by five different anti-HBc assays. Eighty percentage of samples reactive in Architect anti-HBc assay were positive by the Murex assay and anti-HBc neutralization. Eleven out of 397 samples showed discordant results in supplementary testing from the Murex confirmatory test result, and five remained undetermined following extensive serological testing. Thirty-eight percentage of anti-HBc-positive donors identified as minority ethnic groups compared with 11% representation in anti-HBc-negative donors (p < 0.0001); the frequency of the Ro blood group in anti-HBc-positive donors was 18 times higher in non-white ethnic groups. Using two anti-HBc assays effectively enabled the identification of HBV-exposed and potentially infectious donors, their deferral and potential clinical follow-up. However, the exclusion of confirmed anti-HBc-positive donors will still impact the supply of rare blood such as Ro.

Injectable thermogel incorporating reactive oxygen species scavenger and nitric oxide donor to accelerate the healing process of diabetic wounds

The healing of diabetic wounds is challenging due to redox imbalances. Herein, the thermogelling system AR-ACP hydrogel, with encapsulated biosafe nitric oxide (NO) donor L-arginine and resveratrol as an ROS scavenger, is established for sustainable wound therapy in the diabetic state. The innovated AR-ACP hydrogel dressings shows the sol–gel transition at 34 °C, allowing the hydrogel to fully cover wounds. The combination of L-arginine and resveratrol showed a prominent effect on anti-oxidative activity. The elimination of superoxide anions from the activated immune cells/oxidative cells by resveratrol maintained the NO-proangiogenic factors generated from L-arginine. Furthermore, the AR-ACP hydrogel endowed outstanding features such as haemocompatibility, non-skin irradiation as well as antibacterial activity. In the in vivo diabetic mice model, complete epidermal regeneration comparable to undamaged skin was observed with AR-ACP hydrogel. The synergy between L-arginine and resveratrol in the ACP hydrogel facilitated neovascularisation in the early stage, resulting in the higher balance in cellularity growth and collagen deposition in the dermal layer compared to control groups. Taken together, our findings demonstrate that the use of a customised ACP-based hydrogel, with the additional L-arginine and resveratrol, resulted in significant skin regeneration in the diabetic state.

India's Strategic Foreign Aid: 'The China Factor' in India's Foreign Aid Allocation

Foreign aid is known to be the primary means through which governments assist each other. Beyond the altruistic incentives for such help, however, there is self-interest involved. Consequently, foreign aid is not always directed towards the states who need it the most, but rather to those, who can contribute to the donor’s strategic considerations. India is one of the emerging countries, which over the past three decades has been expanding its foreign aid in scale and scope. The rationale behind such foreign policy move by New Delhi is argued to be improving India’s international standing. Its biggest rival China, however, is rapidly expanding its own influence and is stepping into India’s strategic space. In this paper we argue that ongoing emerging power rivalry with China is a key determinant in New Delhi’s foreign aid allocation decisions. we analyse India’s foreign assistance for the period 2015-2020 and look for the ‘China factor’ in its allocation strategies. The cases of the Maldives and Mauritius provide evidence for the main argument and show India as a ‘reactive donor’.

Red blood cells from endothelial nitric oxide synthase-deficient mice induce vascular dysfunction involving oxidative stress and endothelial arginase I

Background & aimsNitric oxide bioactivity (NO) from endothelial NO synthase (eNOS) importantly contributes to the maintenance of vascular homeostasis, and reduced eNOS activity has been associated with cardiovascular disease. Emerging evidence suggests interaction(s) between red blood cells (RBCs) and the endothelium in vascular control; however, the specific role of RBC eNOS is less clear. We aimed to investigate the hypothesis that a lack of RBC eNOS induces endothelial dysfunction. Methods & ResultsRBCs from global eNOS knockout (KO) and wildtype (WT) mice were co-incubated ex vivo overnight with healthy mouse aortic rings, followed by functional and mechanistic analyses of endothelium-dependent and independent relaxations. RBCs from eNOS KO mice induced endothelial dysfunction and vascular oxidative stress, whereas WT RBC did not. No differences were observed for endothelium-independent relaxations. This eNOS KO RBC-induced endothelial dysfunctional phenotype was prevented by concomitant co-incubation with reactive oxygen species scavenger (TEMPOL), arginase inhibitor (nor-NOHA), NO donor (detaNONOate) and NADPH oxidase 4 (NOX4) inhibitor. Moreover, vessels from endothelial cell-specific arginase 1 KO mice were resistant to eNOS KO-RBC-induced endothelial dysfunction. Finally, in mice aortae co-incubated with RBCs from women with preeclampsia, we observed a significant reduction in endothelial function compared to when using RBCs from healthy pregnant women or from women with uncomplicated gestational hypertension. ConclusionsRBCs from mice lacking eNOS, and patients with preeclampsia, induce endothelial dysfunction in adjacent blood vessels. Thus, RBC-derived NO bioactivity acts to prevent induction of vascular oxidative stress occurring via RBC NOX4-derived ROS in a vascular arginase-dependent manner. Our data highlight the intrinsic protective role of RBC-derived NO bioactivity in preventing the damaging potential of RBCs. This provides novel insight into the functional relationship between RBCs and the vasculature in health and cardiovascular disease, including preeclampsia.

UTILITY OF MINI-POOL NAT STRATEGY FOR IMPROVING BLOOD SAFETY BY DETECTING OCCULT HEPATITIS B VIRUS INFECTION : A 5 YEAR STUDY

Introduction: The prevalence of transfusion transmitted infections (TTIs) is high in India. The aim of our study was to evaluate the sero-prevalence of TTIs using Nucleic acid technology (NAT) and detection of Occult Hepatitis B virus infection by Minipool NAT Strategy. A total of 89,639 units of blood donated at Dhanvanta Materials and Methods: ri Voluntary Blood Bank, Rajahmundry during the period from January 2012 to July 2016. The sero-prevalence for HIV, HBV and HCV was tested by 4th generation ELISA. Only sero-negative samples were tested on mini pool nucleic acid test (MP-NAT) to detect HIV1, HIV2, HCV and HBV viral nucleic acids. Combined NAT yield was calculated and compared the NAT yield with MPX test and MPX V2.0. We also evaluated the optical density (OD) values of ELISA for MP-NAT reactive donor samples to evaluate the efcacy of NAT in detecting window period cases. The Results: overall sero-prevalence of TTIs was 2.41% and HBV was predominantly present (66%). Total 29 ELISA negative blood donor samples were found reactive on NAT. All NAT reactive donors were of HBV only. Out of 29 cases, 12 were detected by MPX test from 26,008 donations and 17 by MPX V2.0 from 25,619 donations, providing NAT yield of 1:2169 and 1:1507 respectively. OD and Signal cut off values of ELISA for NAT reactive samples were found to be much below extended grey zone value (&lt;0.3). Additiona Conclusion: l testing of nucleic acids by MP-NAT in combination of mandated primary serology by ELISA provides 99.99% of safe blood to needy patients; thus signicantly reduces the risk of TTIs by identifying the window period cases.

Correlation of serological and molecular markers in the screening for hepatitis B virus in blood bank in northern Brazil

IntroductionIn Brazil, the blood donor screening for hepatitis B virus (HBV) includes laboratory testing for serological (HBsAg and Anti-HBc) and molecular (HBV DNA) markers. This study aims to correlate serology reactive results with HBV DNA detection among blood donors with at least one HBV infection marker detected in a blood bank in northern Brazil. MethodA retrospective search for HBV reactive blood donor data from January 2017 to December 2019 was performed. Serological screening was performed by chemiluminescent microparticle immunoassays Architect HBsAg and Architect Anti-HBc, whereas molecular screening was performed by the HBV nucleic acid test (HBV NAT). Main resultsA total of 556 HBsAg reactive results were detected, between positive (47.66%) and inconclusive (52.34%). A total of 3,658 Anti-HBc reactive results were detected, between positive (83.71%) and inconclusive (16.29%). None of the inconclusive results were associated with HBV DNA detection. The HBV DNA detection rates were 47.55% among HBsAg positive samples and 4.08% among Anti-HBc positive samples. The signal-to-cutoff (S/CO) ratio median of HBV NAT positive samples was superior in comparison to HBV NAT negative samples (p < 0.0001). The thresholds found to optimize sensitivity and specificity were 404.15 for Architect HBsAg and 7.77 for Architect Anti-HBc. Three blood donors were in the window period and 1 occult HBV infection case was detected. ConclusionHigh S/CO ratios were more predictive of HBV DNA detection. However, a number of HBV NAT positive samples gave low values, while some HBV NAT negative samples showed high values, reaffirming the significance of molecular testing to enhance transfusion safety.

Reverse algorithm for screening of syphilis and trends in prevalence among blood donors in Coastal Karnataka.

Transfusion transmissible syphilis is caused by Treponema pallidum; blood donors are traditionally screened with non-treponemal antibody tests to ensure transfusion safety. Detection of specific antibodies against T. pallidum is employed in reverse algorithm screening. We aim to analyze the utility of the reverse algorithm screening strategy for T. pallidum and to determine the prevalence trends among blood donors in our centre. The study was conducted in a Transfusion Centre catering to the 2030 bedded Tertiary Care Centre in coastal Karnataka in two timelines from 2012 to 2014, and 2019 to 2020, respectively. A fully automated Enzyme-Linked Immunosorbent Assay and Enhanced Chemiluminescence Immunoassay, which detect both IgM and IgG antibodies against T.pallidum were used in the study. Blood donor data from 2008 to 2020 were also analyzed to observe the trend in prevalence rate of syphilis among blood donors. Among 26329 and 388 blood donors screened with ELISA and ECI, 134 (0.51%) and 9 (2.3%) were reactive to T. pallidum antibodies respectively. TPHA confirmed that 104 and 9 donors were reactive from each of the ELISA and ECI reactive donor groups. The increase in the prevalence of syphilis was observed with the use of reverse algorithm compared to the traditional strategy. The prevalence of syphilis in the present study ranged from 0.02 to 0.28%. The reverse algorithm screening can give a better result with a positive predictive value of 77.61% and 88.9% for ELISA and ECI. respectively Our study found that the use of reverse algorithm might increase the blood discard rate slightly but adds on to safety of blood components.

Pemeriksaan Antibody Dengue Pada Darah Donor di PMI Kabupaten Sleman Dengan Metode Rapid Test

Dengue Hemorrhagic Fever (DHF) is a disease caused by Dengue Virus (DENV), which concluding serotypes (1-4) through mosquito bites and transmitted into humans. DHF is endemic and has increasing cases every year in almost every region in Indonesia, such as Kabupaten Sleman. Currently, screening for Infectious Diseases Transmitted by Blood Transfusion in blood donor only requires Hepatitis B, Hepatitis C, HIV, and Syphilis, despite any other diseases such as Dengue. Therefore, this study needs to detect the IgG/IgM Dengue antibodies on blood donor obtained from PMI Sleman to ensure safety and good quality of blood donor. This research method is used descriptive observational research and the samples are obtained from PMI Sleman. Examining for Dengue IgG/IgM antibodies for donor blood samples was accomplished by the rapid test method. The results showed that all blood donor samples were non-reactive from Hepatitis B, Hepatitis C, HIV, and Syphilis as Infectious Diseases Transmitted by Blood Transfusion. There were 16 (51,72%) blood samples that were reactive of IgG/IgM Dengue and 13 (44,83%) blood samples were non-reactive IgG/IgM Dengue. The reactive blood samples divide into four blood groups, there were 7 (24,14%) samples of blood type A,Rh+; 1 (3,45%) sample of blood type B, Rh+; 2 (6,90%) samples with blood type B,Rh+; 2 (6,90%) samples with blood type AB,Rh+ and 6 (20,69%) samples with blood type of AB, Rh+. Moreover, the reactive donor blood samples divide as 15 (24,14%) samples were in the 17-30 years-old age group and there was 1 (3,45%) was from the 31-40 years-old age group.

Impact of notification and counselling of reactive blood donors at a super-speciality hospital

Background: Donor notification is emphasized as an efficient method of curtailing TTIs recently. But its limitations like low notification rate and lack of follow up of treatment of notified donors are still unaddressed. The aim of the study was to analyze the response rate of notified reactive donors, to elicit hidden risks factors and to see impact of donor notification on reactive donors.Methods: This retrospective study was conducted in the blood bank of a 350 bedded multispecialty hospital in north India. Data was collected from reactive blood donor counselling register over a period of one year. After six months a telephonic interview was conducted of all the reactive donors who responded to notification calls and came for counselling to inquire if they went for further testing and treatment after they were notified.Results: There were 1345 whole blood donations over a period of 14 months of which 29 (2.15%) were reactive donors. Notification rate was 48.27%. During counselling 4 donors revealed high risk history which they had denied during pre-donation counselling. After telephonic conversation with these notified donors, we analyzed that 7 (50%) donors were taking treatment while 3 donors informed that they got themselves tested from a private lab and were reported negative. Two donors informed that they had not gone for any testing anywhere while we could not trace 2 donors due to change of contact numbers.Conclusions: Curtailing TTI’s through donor notification by blood banks alone is an unattainable mission. A centralized computer data system connecting all blood banks and interlinking of government agencies and blood banks like the recently started NVHCP is need of the hour.

Seroprevalence of anti-severe acute respiratory syndrome coronavirus 2 antibody among healthy blood donors in a hospital-based blood center in Eastern India during the COVID-19 pandemic.

BACKGROUND:Few international studies have reported the prevalence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in healthy, asymptomatic blood donors. These findings have definitely raised queries regarding blood safety and transfusion-transmitted coronavirus disease (COVID)-19. We conducted this first anti-SARS-CoV-2 seroprevalence survey among the healthy blood donors in Eastern India.MATERIALS AND METHODS:The study included 611 healthy blood donors who donated whole blood (WB) in our blood center. For detailed analysis, social and demographic details of all donors like gender, age, weight, occupation, and place of residence were included. Donor eligibility criteria for WB donation were followed as per existing national guidelines. Residual serum samples leftover after screening the mandatory infectious markers were tested for the presence of anti-SARS-CoV-2 IgG directed against domain S1 and S2 of the SARS-CoV-2 spike protein using automated enhanced chemiluminescence technology following the manufacturer's instructions.RESULTS:The mean overall seroprevalence of anti-SARS-CoV-2 antibody in blood donors was observed to be 4.4% (95% confidence interval 3.8–4.9) with a monthly increasing trend. Seroprevalence adjusted for sensitivity and specificity of the assay was 4.1%. The mean S/Co values of reactive donor samples were observed to be 2.99 and 3.42 in June and July 2020, respectively (P = 0.013). No significant variation in seroprevalence rate was observed among donor variables like donor age, gender, profession, and educational qualification. A higher significant prevalence of antibody was observed among voluntary donors and donors residing in suburban areas (P < 0.05). Among the ABO blood groups, no statistical significance of seroprevalences was observed among the various ABO blood groups.CONCLUSION:We conclude that despite many limitations in the current study, we found 4.4% seroprevalence of anti-SARS-CoV-2 antibody in the asymptomatic, healthy, epidemiologically, and medically screened blood donors. These data are definitely the tip of an iceberg and signify much higher seroprevalence in the normal population and indicate that protective measures like masking and social distancing should remain implemented for a long term.

Synthesis of Benzoisoselenazolones via Rh(III)-Catalyzed Direct Annulative Selenation by Using Elemental Selenium.

Isoselenazolone derivatives have attracted significant research interest because of their potent therapeutic activities and indispensable applications in organic synthesis. Efficient construction of functionalized isoselenazolone scaffolds is still challenging, and thus new synthetic approaches with improved operational simplicity have been of particular interest. In this manuscript, we introduce a rhodium-catalyzed direct selenium annulation by using stable and tractable elemental selenium. A series of benzamides as well as acrylamides were successfully coupled with selenium under mild reaction conditions, and the obtained isoselenazolones could be pivotal synthetic precursors for several organoselenium compounds. Based on the designed control experiments and X-ray absorption spectroscopy measurements, we propose an unprecedented selenation mechanism involving a highly electrophilic Se(IV) species as the reactive selenium donor. The reaction mechanism was further verified by a computational study.

Evaluasi uji saring hepatitis B reaktif pada darah donor tahun 2019 di UTD PMI kota Malang

Background: Screening tests for infectious infections through blood transfusion (IMLTD) are one of the blood safeguards carried out at the Blood Transfusion Unit. Hepatitis B is one of the infectious diseases that must be examined.&#x0D; Objective: It aims to evaluate IMLTD, identify the types of donors that show reactive hepatitis B based on new donors and routine donors, identify causes based on input, process, output whether true or false reactive, and counseling reactive donors.&#x0D; Methods: Descriptive research with a quantitative approach. Population is 49,379 donors in 2019 (0.0052%), sample is 256 donors. Primary and secondary data were taken at UTD PMI Malang City then a questionnaire was made and an evaluation was carried out.&#x0D; Results: Evaluation of reactive hepatitis B screening tests based on the evaluation of the number of blood donors with reactive hepatitis B obtained the types of donors, namely new donors (55%) and routine donors (44%). Evaluation based on input and output obtained donor blood samples according to the required criteria (100%). Evaluation process for officers, methods, reagents, and room conditions with good results (100%), while the suitability of the tools (97.23%). Hepatitis B reactive donors who did counseling (17.2%).&#x0D; Conclusion: UTD PMI Malang City which has been certified CPOB BPOM RI can maintain the quality and consistency of the quality of blood services, especially in the hepatitis B reactive donor counseling service. Evaluation results of hepatitis B filter test are true reactive and consistency is needed in maintaining quality policy is needed for donor counseling.

Gambaran Hasil Pemeriksaan HIV pada Darah Donor

HIV cases in Jepara District in recent years have demanded the handling of several aspects simultaneously including the Blood Transfusion Unit (BTU). HIV can be transmitted through blood transfusion or other blood products. BTU of PMI Jepara Regency carries out recruitment of voluntary donor from Jepara society. The HIV examination as part of an IMLTD screening test is done for safety of donor blood. The HIV examination in all donor blood uses rapid and elisa method. Examination results are stated as reactive and non reactive. Research objective to find out the description of HIV examination results in donor blood at the BTU of PMI Kabupaten Jepara in 2019. Research method the research type was descriptive using records of donor data at BTU of PMI Kabupaten Jepara in 2019. The examination results of reactive HIV in 12 donor blood (0,08%). non-reactive blood donor of HIV in age groups 18 years, 18-24, 25-44, 45-59, and ≥ 60 years respectively 9,55%, 22,39%, 51,75%, 16,01% and 0,21%. Reactive HIV in age groups 18-24, 25-44, and 45-59 years were 0,034%, 0,034%, and 0,13%. Non-reactive HIV in men 68,22% and in women 31,70%. Reactive HIV in men 0,07%, and women 0,01%. Non-reactive HIV in voluntary donor blood was 99,779% and substitute donor was 0,127%. HIV of reactive voluntary donor blood was 0,074%, and substitute donor was 0,007%. HIV filter test is indispensable for blood safety because the age, gender and blood type of donors have the potential for reactive HIV.

Post-transplant cyclophosphamide limits reactive donor T cells and delays the development of graft-versus-host disease in a humanized mouse model.

Graft-versus-host disease (GVHD) is a major complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT) that develops when donor T cells in the graft become reactive against the host. Post-transplant cyclophosphamide (PTCy) is increasingly used in mismatched allo-HSCT, but how PTCy impacts donor T cells and reduces GVHD is unclear. This study aimed to determine the effect of PTCy on reactive human donor T cells and GVHD development in a preclinical humanized mouse model. Immunodeficient NOD-scid-IL2Rγnull mice were injected intraperitoneally (i.p.) with 20×106 human peripheral blood mononuclear cells stained with carboxyfluorescein succinimidyl ester (CFSE) (day 0). Mice were subsequently injected (i.p.) with PTCy (33mgkg-1 ) (PTCy-mice) or saline (saline-mice) (days 3 and 4). Mice were assessed for T-cell depletion on day 6 and monitored for GVHD for up to 10weeks. Flow cytometric analysis of livers at day 6 revealed lower proportions of reactive (CFSElow ) human (h) CD3+ T cells in PTCy-mice compared with saline-mice. Over 10weeks, PTCy-mice showed reduced weight loss and clinical GVHD, with prolonged survival and reduced histological liver GVHD compared with saline-mice. PTCy-mice also demonstrated increased splenic hCD4+ :hCD8+ T-cell ratios and reduced splenic Tregs (hCD4+ hCD25+ hCD127lo ) compared with saline-mice. This study demonstrates that PTCy reduces GVHD in a preclinical humanized mouse model. This corresponded to depletion of reactive human donor T cells, but fewer human Tregs.

MO982COMPARISON OF BASILIXIMAB AND R-ATG ON ACUTE REJECTION RISK IN HIGH IMMUNOLOGICAL RISK RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims High Panel Reactive Antibody (PRA) level has been widely accepted as a marker for acute rejection risk following kidney transplantation. PRA&amp;gt;/= 20% is considered a high immunological risk renal transplant. The aim of our study was to assess the risk of acute rejection in kidney transplant recipients (KTR) following Basiliximab induction compared to Rabbit Anti-Thymocyte Globulin (R-ATG) maintained on tacrolimus and mycophenolate mofetil maintenance immunotherapy. Method This was a retrospective observational cohort study using data from the United States Organ Procurement and Transplantation Network, all KTR’s with PRA =/&amp;gt; 20%, who were maintained on tacrolimus and mycophenolate mofetil between September 2017 and September 2019 were included. Follow-up was until September 2020. Data included recipient factors (age, sex, ethnicity, diabetes, body mass index), transplant factors (delayed graft function, cold ischemia time, number of previous transplants, panel reactive antibodies, HLA-mismatches, induction therapy, maintenance immunotherapy and donor factors (donor type, donor age). The cohort were divided into 2 groups; living and deceased donor renal transplants. The groups were further divided by PRA level, each group was divided into 3 subgroups: Group A (low PRA level: PRA range from 20% to 49%), Group B (moderate PRA level: PRA range from 50% to 79%), and Group C (High PRA level: PRA range from 80% to 100%). Multivariable logistic regression models were constructed to assess the effect of induction therapies (Basiliximab versus R-ATG) on acute rejection episodes at 6 months post-transplant. The multivariable model was adjusted for recipient, donor and transplant factors mentioned above. Results Among living donor KTR’s, there was no difference between Basiliximab and R-ATG in acute rejection episodes in any of the three groups, Group A (low PRA level, n=717, OR=1.17, P=0.79, 95%CI:0.34-3.95), Group B (moderate PRA level, n=618, OR=1.51, P=0.58, 95%CI:0.33-6.92) and Group C (high PRA level, n=401, OR=1.17, P=0.85, 95%CI:0.21-6.56) respectively. In contrast, among deceased donor KTR’s R-ATG was associated with lower risk of rejection compared to Basiliximab in all three groups, group A (low PRA level, n=1895, OR=0.52, P=0.03, 95%CI: 0.28-0.94), group B (moderate PRA level, n=1618, OR=0.41, P&amp;lt;0.01, 95%CI: 0.22-0.78) and group C (high PRA level, n=3973, P&amp;lt;0.01, 95%CI: 0.28-0.70). Conclusion This study shows that risk of acute rejection is no different with Basilximab induction compared to R-ATG in high immunological risk living-donor KTR’s at all levels of PRA in the current tacrolimus-mycophenolate mofetil immunosuppression era. However, risk of acute rejection seems to be lower in deceased donor KTR’s having R-ATG induction at all levels of PRA. Delayed graft function is a risk factor for acute rejection, our models did not adjust for dose of R-ATG which may explain the lower risk seen in deceased donor KTR’s, data was not available on donor specific antibodies. In summary, Basiliximab induction has similar acute rejection rates as R-ATG in living donor KTR’s whereas in deceased donor KTR’s R-ATG was found to be better.

MO980OUTCOMES OF RABBIT ANTI-THYMOCYTE GLOBULIN VERSUS IL-2 RECEPTOR ANTAGONIST INDUCTION THERAPIES IN 2DR MISMATCH RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims 2DR HLA mismatch indicates high immunological risk renal transplant. Induction therapy with rabbit Anti-thymocyte Globulin (r-ATG) and IL-2 Receptor Antagonist (IL-2RA) resulted in marked reduction of acute allograft rejection rate and improved graft survival. However, the outcomes in 2DR (HLA-DR) mismatched renal transplant recipients (RTRs) in the era tacrolimus-mycophenolate mofetil maintenance immunosuppression remains understudied. Method This was a retrospective cohort study using data from the United States Organ Procurement and Transplantation Network, all 2 DR mismatched RTRs who were maintained on tacrolimus and mycophenolate mofetil immunotherapy between 2005 and 2015 were included. Follow up data was until September 2020. Patients who received transplants from living donors were included in the study. Collected data included recipient factors (age, sex, ethnicity, diabetes, body mass index), transplant factors (delayed graft function, cold ischemia time, number of previous transplants, panel reactive antibodies, HLA-mismatches, induction therapies, maintenance immunotherapy, and donor factors (donor type, donor age). RTRs were divided into 2 groups: based on induction therapy r-ATG and IL-2RA. Instrumental variable regression models were used to assess effect of induction therapy on acute rejection episodes at 6 months post-transplant and on graft survival. Type of induction therapy was instrumented for the transplant centre to reduce the centre effect on the choice of the induction therapy. Cox proportional hazard regression analysis was performed to assess the effect of induction therapy on graft survival. The regression models were adjusted for collected recipient, donor and transplant factors. Results 3052 patients received IL2-RA while 5143 patients received R-ATG induction. Using instrumental variables regression models, there were no significant differences between IL2-RA versus R-ATG induction in acute rejection episodes (OR=1.49, 95% CI ranges from 0.73 to 3.05, P=0.27), or graft survival (coefficient=0.95, 95% CI: -0.18 to 2.10, P=0.10). Using Cox proportional hazards regression, there was no significant difference in graft survival between either induction therapies (HR=0.90, 95% CI: 0.74 to 1.09, P=0.29). Conclusion This study showed no significant difference in acute rejection episodes or graft survival when using ATG or IL-2RA in 2DR HLA mismatched renal transplant recipients in the current tacrolimus-based maintenance immunosuppression era. Therefore, IL2-RA is a safe induction therapy in this group of patients and non-inferior to R–ATG induction therapy. Moreover, this study also highlights the fact that antigen level 2DR mismatches are not a risk factor for rejection and HLA matching should be based on epitope level rather than antigen level.